The key focus of the pharmaceutical or chemical industries is to reduce the cost involved in the development of new drugs and to improve the selectivity, sensitivity, and resolution for their detection. The purpose can now be solved by the separation method called UPLC which is the modified HPLC method comprising high pressure and small sized particles (less than 2 µm) used in the column, so the length of the column decreases leading to time saving and reduction in the consumption of solvent. The underlying principle of UPLC is based on van Deemter statement which describes the connection between linear velocity with plate height. UPLC contributes to the improvement of the three areas: speed, resolution, and sensitivity. This is a new advanced category of the HPLC which has the same basic principle and methodology with improved chromatographic performance. This review is an effort to compile the principle, instrumentation, and applications of UPLC.